Precision medicine is a broad concept, going far beyond the singular use of genomic or other molecular markers of health and disease susceptibility. We are unique in ways that were not characterized even a decade ago; our health and healthcare must be viewed and delivered in more nuanced ways than is currently possible. The development of the harmonizing programs under the new Precision Medicine Initiative (PMI) now puts this goal within reach. It is with this spirit that we submit this proposal to serve as the PMI Preparatory/Prototyping Initiative (or Pi) for the Direct Volunteers (DV) Pilot Studies. The team we have mobilized is made up of individuals who have an outstanding record of accomplishment in the diverse disciplines needed to bring this proposal to life, and who embrace the PMI?s scientific vision, which shapes the essential methodologies of implementation. The leadership will be at Vanderbilt with synergistic national partners including the Broad Institute, Verily (formerly Google Life Sciences), and the University of Michigan. Each of our organizations will also be part of applications for the future Centers, so we have especially strong motivations to produce high quality prototypes and methods. Our passion for the promise of precision medicine, throughout the entire translational spectrum, has catalyzed development of internationally-recognized programs enabling genomic discovery,1?4 clinical implementation,5,6 population engagement (e.g. ResearchMatch, Genes for Good), and multi-institutional secure and robust scientific collaborations (REDCap, IRBshare, Accelerated Clinical Trial Agreement). It inspires our active participation in national networks that are deciphering the interactions of the human phenome and genome and actively exploring ways by which this new knowledge can most swiftly improve health. It has molded the careers of a critical mass of engaged faculty at each organization. This RFA has the shortest time to deadline to which we have ever responded. We do so with enthusiasm and confidence in our ability to execute immediately upon award ? the components are in place